PT  - JOURNAL ARTICLE
AU  - Franck Dumetz
AU  - Eugene Yui-Ching Chow
AU  - Lynne M. Harris
AU  - Mubarak I. Umar
AU  - Anders Jensen
AU  - Betty Chung
AU  - Ting Fung Chan
AU  - Catherine J. Merrick
AU  - Chun Kit Kwok
TI  - G-quadruplex RNA motifs influence gene expression in the malaria parasite <em>Plasmodium falciparum</em>
AID  - 10.1101/2021.03.08.434398
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.03.08.434398
4099  - http://biorxiv.org/content/early/2021/03/08/2021.03.08.434398.short
4100  - http://biorxiv.org/content/early/2021/03/08/2021.03.08.434398.full
AB  - G-quadruplexes are non-helical secondary structures that can fold in vivo in both DNA and RNA. In human cells, they can influence replication, transcription and telomere maintenance in DNA, or translation, transcript processing and stability of RNA. We have previously showed that G-quadruplexes are detectable in the DNA of the malaria parasite Plasmodium falciparum, despite a very highly A/T-biased genome with unusually few guanine-rich sequences. Here, we show that RNA G-quadruplexes can also form in P. falciparum RNA, using rG4-seq for transcriptome-wide structure-specific RNA probing. Many of the motifs, detected here via the rG4seeker pipeline, have non-canonical forms and would not be predicted by standard in silico algorithms. However, in vitro biophysical assays verified the formation of non-canonical motifs. The G-quadruplexes in the P. falciparum transcriptome are frequently clustered in certain genes and associated with regions encoding low-complexity peptide repeats. They are overrepresented in particular classes of genes, notably those that encode PfEMP1 virulence factors, stress response genes and DNA binding proteins. In vitro translation experiments and in vivo measures of translation efficiency showed that G-quadruplexes can influence the translation of P. falciparum mRNAs. Thus, the G-quadruplex is a novel player in post-transcriptional regulation of gene expression in this major human pathogen.Competing Interest StatementThe authors have declared no competing interest.